The immense impact of the fMRI technique on the neuroscience community, which allows noninvasive localization of active cortical regions, is well reflected by the exponential increase of publications utilizing this technique. For the past decade, great effort has been put into increasing the spatial resolution and specificity of fMRI signals from vessel-weighted to more tissue specific signals. The working assumption is that the "tissue" signals closely mirror changes at the neuronal level. While great progress has been made, the basic and most fundamental questions remain unanswered: Where in the tissue do these "tissue-fMRI" changes occur? Do they indeed originate at the site of the most active neurons/layer? The aim of this study is to identify the spatial and anatomical origin of the fMRI signals to the level of cortical layers. In this proposed study we will correlate high-resolution fMRI signals (0.15 x 0.15 mm2) with the underlying cortical laminar cytoarchitectonic and microvascular structures in the same animal and cortical section. In this proposal a new method for identifying and extracting the exact cortical tissue corresponding to the fMRI plane will be developed. Once extracted, the corresponding cortical slab will undergo standard histological staining procedures to uncover the laminar and vascular structures. Thus, based on histological criteria obtained from the matching tissue, the spatial origin of tissue fMRI hemodynamic signals will be determined. The impact and outcome of this study will greatly enhance our understanding of the fMRI signal source. This in return will open the opportunity to study brain function and cerebral hemodynamic regulation at the laminar resolution, levels that are currently unattainable.